Research Interests:
The goals of my research program are to better understand virus structure, function, assembly, and pathogenesis.

We have been using mammalian reoviruses (MRV) and avian reoviruses (ARV) as models for understanding how multiple proteins and nucleic acids recognize each other and interact to generate a functionally active macromolecular complex. We have generated and characterized sets of assembly-defective temperature-sensitive (ts) mutants. These mutants, as well as normal wild-type virus, are being examined by biologic, molecular genetic, and mass spectroscopic methods to better understand virus assembly and disassembly. We also are conducting a variety of functional assays of viral RNA-dependent RNA polymerase, an enzyme unique to virtually all RNA viruses but absent from host cells to aid development of therapeutic strategies to combat RNA viruses.

Viruses induce profound changes in cells at both the genomic and protein levels. We are using state-of-the-art Systems Biology approaches, such as quantitative and comparative mass spectrometry, shRNAi, and Activity-Based Protein Profiling to understand the effects induced in the total cellular Proteome (entire protein repertoire, including all modifications) after various cells are infected with either reoviruses or influenza viruses.

There are numerous strategies to combat infections by pathogenic organisms, including vaccination and anti-virals. We are testing the capacities of various anti-viral compounds to attenuate replication of reoviruses and influenza virus. We also are interested in selecting anti-viral-resistant mutants of each virus type to better understand molecular mechanisms of antiviral effects and resistance mechanisms.

Viruses are the primary cause of infectious gastroenteritis and, importantly, many cases are caused by unknown viruses. Thus, we also seek to discover and molecularly characterize novel viral agents. We have discovered two such potentially new viruses that are currently under molecular analyses to allow comparison to other known agents and to establish diagnostic and therapeutic strategies.

Recent work by Dr. Patrick Lee at the University of Calgary has shown that reovirus may have potential as an anti-cancer agent. To be used therapeutically, it will be necessary to grow industrial-sized quantities, and, because of dangers associated with bovine spongiform encephalopathies ("mad cow disease"), preferably in growth media devoid of animal products. In collaboration with Dr. Mike Butler in the Department of Microbiology at our University, we have been experimenting with growing industrial-sized amounts of virus in serum-free media.

There is increased concern about the safety of available drinking water and environmental consequences of contaminated waste water and water runoff. In collaboration with Dr. Jan Oleszkiewicz, of the Department of Engineering, we are using the MRV as a “bio-indicator” to test the efficiency of various treatments during disinfection of water and wastewater.

There also is increased concern about decontaminating medical devices. In collaboration with Dr. Michelle Alfa we are also using MRV “bio-indicators” to test various methods for decontaminating endoscopes and other medical devices.